In yeast and other microorganisms, the chain elongation reaction of fatty acids occurs through four steps, i.e., (i) condensation reaction between fatty acid acyl-CoA and malonyl-CoA, (ii) reduction reaction of the condensation product 3-oxoacyl-CoA, (iii) dehydration reaction of 3-hydroxyacyl-CoA, and (iv) reduction reaction of trans-2-enoyl-CoA, whereby the number of carbon atoms is increased by two per cycle of these steps to elongate the chain length (Non-patent Document 1).
The reactions in the above steps (i) to (iv) are known to be catalyzed by enzymes (i) 3-ketoacyl-CoA synthase, (ii) β-ketoacyl reductase, (iii) 3-hydroxyacyl-CoA dehydrogenase, and (iv) enoyl-CoA reductase, respectively (Non-patent Document 1).
Among these enzymes, 3-ketoacyl-CoA synthase which is responsible for condensation reaction is known to have specificity with respect to fatty acids serving as substrates, and enzymes having different specificities have been cloned from various organisms.
In particular, in yeast which has been most well studied among fungi, for all the four steps of fatty acid chain elongation reaction, there have been identified an enzyme responsible for the reaction in each step and a gene encoding the same.
For example, there are two genes IFA38 and AYR1 in yeast, each of which is known to encode an enzyme responsible for β-ketoacyl reductase activity, and it is further known that simultaneous deletion of both genes is lethal (Non-patent Document 2). Moreover, the AYR1 gene is also known to have 1-acyl dihydroxyacetone phosphate reductase activity (Non-patent Document 3).
On the other hand, PHS1 (essential) is known as a gene encoding an enzyme responsible for 3-hydroxyacyl-CoA dehydrogenase activity, while TSC13 (essential) is reported as a gene encoding an enzyme responsible for enoyl-CoA reductase activity.
In contrast, a lipid-producing fungus, Mortierella alpina (M. alpina)), is known to have 3-ketoacyl-CoA synthase (so-called elongase) genes (MALCE1 (ELO3), MALCE2, GLELO, MAELO) responsible for the first reaction involved in fatty acid chain elongation (Patent Document 1), although genes for enzymes other than 3-ketoacyl-CoA synthase have not yet been identified.